Delineating human norovirus tropism at the single cell level

Sue Crawford, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX

1. Luqiong Wang, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; 2. Khalil Ettayebi, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; 3. Tajhal Patel, Texas Children's Cancer and Hematology Centers and The Faris D. Virani Ewing Sarcoma Center, Baylor College of Medicine, Houston, TX; 4. Carolyn Bomidi, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; 5. Sue E. Crawford, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; 6. Sasirekha Ramani, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX; 7. Cristian Coarfa, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX; 8. Mary K. Estes Department of Molecular Virology and Microbiology, Department of Medicine, Baylor College of Medicine, Houston, TX; 9. Sarah E. Blutt, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX

Structure & Pathogenesis

Human noroviruses (HuNoVs) are the leading viral cause of acute gastroenteritis worldwide. Given the substantial healthcare costs and economic burden caused by HuNoV infections and the lack of approved vaccines or antiviral therapies, there is a need for a deep understanding of HuNoV infection and host interactions. Cellular tropism is critical for viral pathogenesis. However, the cellular tropism for HuNov has not yet been fully elucidated. While previous investigations have demonstrated that enterocytes are the predominant cell type susceptible to HuNoV infection, recent studies showed that enteroendocrine cells are also permissive to HuNoV, suggesting that HuNoVs may have yet unexplored cellular targets. Notably, these studies used biopsies from immunocompromised transplant patients, leaving the question of what are the cellular targets in immunocompetent patients unanswered. The development of human intestinal organoids (HIOs) as an ex-vivo model for HuNoV cultivation has provided tremendous insights into HuNoV replication and pathogenesis. To elucidate the HuNoV cell tropism, we infected HIOs with a globally dominant GII.4 HuNoV strain and utilized single-cell RNA sequencing to comprehensively profile transcriptomic changes at the single-cell resolution. This approach identified unique cell clusters containing viral transcripts as well as key genes and pathways elicited in response to infection. Our next step is to delineate cell type specific responses and cellular factors contributing to their susceptibility to viral disease. Overall, this project has the potential to significantly advance our knowledge of HuNoV infection biology, laying a foundation for future investigations into the development of effective interventions.